Synopsis: The data from this study provide the most conclusive evidence to date that postmenopausal hormone use slows the age-related gain in weight.

Despite recent studies showing that the effect of postmenopausal hormone use upon body weight is to slightly decrease the rate of age-related gain, most women believe that noncontraceptive hormone use causes weight to increase. The aforementioned investigations suggesting a protective effect of hormones against weight gain involved cross-sectional comparisons, nonrandomized prospective studies, and relatively small clinical trials. Postmenopausal Estrogen/Progestin Intervention trial (PEPI) is a randomized, placebo-controlled, prospective study, with a large sample size of 875 women followed for three years. Thus, it has far greater power than any of the preceding studies. The PEPI study arms were five: conjugated equine estrogens, 0.625 mg daily, with and without progestin exposure, and placebo. There were no differences between the groups that received hormones and, thus, the analysis involved comparing the hormone-treated vs. placebo groups. Of the 875 women, 41% were between 45-54 years, and the rest were between 55-65 years. Four percent were black, 5% Hispanic, 2% Asian, 1% American Indian, and 89% white. Fourteen percent were current smokers, and 37% were former smokers. Women randomized to active therapy gained 1.0 kg less than women randomized to placebo. Both groups tended to gain weight across time, although most of the weight gain occurred between the ages of 45 to 54 years. Increased physical activity was associated with lesser weight gain. The use of any of the progestin regimens (continuous medroxyprogesterone acetate 2.5 mg daily or 5 mg cyclically or oral micronized progesterone cyclically) did not affect weight gain. Smokers did not have the same protection from weight gain as did nonsmokers. In this study, waist girth tended to increase in both groups, but the increase was greater in women assigned to placebo.

n COMMENT BY SARAH L. BERGA, MD

The data from this study provide the most conclusive evidence to date that postmenopausal hormone use slows the age-related gain in weight. Since women tend to gain the most weight in the years just following menopause, which is also the time that they are likely to initiate hormone use, it is understandable that this age-related gain in weight has been attributed to estrogens and progestins. Interestingly, while these data exonerate hormone use as the cause of middle age-related weight increases, the true metabolic culprit has yet to be concretely identified. A recent study suggests that in women, it is not growth hormone. (Khorram O, et al. J Clin Endocrinol Metab 1997;82:1472-1479). As one ages, there is a progressive and generalized loss of muscle mass that may slow the basal metabolic rate and facilitate weight gain if calorie intake is not curtailed. Physical exercise increases muscle mass and enhances metabolic rate, so it is not surprising that the women who were the most physically active gained the least amount of weight.

These data are intellectually interesting and informative, but their presence in this article will do little good if the information is not disseminated. Smokers need to understand that this habit counteracts the many benefits of postmenopausal hormone use. If a smoker fears that quitting will lead to weight gain, it is important for her to understand that that may be less the case in middle age. Although hormone use may have many benefits, what motivates women to comply varies. For some, body image is crucial, and the thought that hormones will cause them to lose the battle of the bulge is all the rationale they need for not taking hormones. Although it is difficult to find the time to understand what patients do and do not know and what motivates them, it is important to try. If they understand that hormone use protects from weight gain, this may be all the rationale they need to try it. (Dr. Berga is Associate Professor of Obstetrics, Gynecology, Reproductive Services, and Psychiatry, University of Pittsburgh.)

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